Levelt C N, Mizoguchi E, Huang X, Zacks R, Bhan A K, Tonegawa S
Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Proc Natl Acad Sci U S A. 1998 Nov 24;95(24):14349-54. doi: 10.1073/pnas.95.24.14349.
The mature T cell receptor (TCR) repertoire is shaped by positive- and negative-selection events taking place during T cell development. These events are regulated by interactions between the TCR and major histocompatibility complex molecules presenting self-peptides. It has been shown that many antagonist peptides are efficient at mediating positive selection. In this study we analyzed the effects of a transgene encoding an antagonist peptide (influenza NP34) that is presented by H-2Db in a Tap-1-independent fashion in mice expressing the influenza NP68-specific TCR F5. We find that the transgenic peptide does not mediate positive or negative selection in F5(+)Tap-1(-/-) mice, but inhibits maturation of CD8(+) single positive thymocytes in F5(+)Tap-1(+) mice without inducing signs of negative selection. We conclude that antagonism of antigen recognition occurs not only at the level of mature T cells but also in T cell development.
成熟的T细胞受体（TCR）库是由T细胞发育过程中发生的阳性和阴性选择事件塑造的。这些事件由TCR与呈递自身肽的主要组织相容性复合体分子之间的相互作用调节。已表明许多拮抗剂肽在介导阳性选择方面很有效。在本研究中，我们分析了编码拮抗剂肽（流感NP34）的转基因的作用，该肽在表达流感NP68特异性TCR F5的小鼠中以不依赖Tap-1的方式由H-2Db呈递。我们发现转基因肽在F5(+)Tap-1(-/-)小鼠中不介导阳性或阴性选择，但在F5(+)Tap-1(+)小鼠中抑制CD8(+)单阳性胸腺细胞的成熟，而不诱导阴性选择的迹象。我们得出结论，抗原识别的拮抗作用不仅发生在成熟T细胞水平，也发生在T细胞发育过程中。
